Integrating next‐generation sequencing into the diagnostic testing of inherited cancer predisposition

The clinical application of next‐generation sequencing (NGS) as a diagnostic tool has become increasingly evident. The coupling of NGS technologies with new genomic sequence enrichment methods has made the sequencing of panels of target genes technically feasible, at the same time as making such an approach cost‐effective for diagnostic applications. In this article, we discuss recent studies that have applied NGS in the diagnostic setting in relation to hereditary cancer.     

Qualitative observation in a clinical setting: Challenges at end of life

This paper explores the methodological challenges associated with undertaking qualitative observation in the clinical setting at end of life. The authors reflect on their experiences of using non‐participant observation to explore the nursing care delivered to dying patients in acute hospital wards. The challenges of observation as a method, clearly defining the participant group and involving vulnerable populations, such as the dying patients and their families, will be discussed. Consideration is also given to defining and working within the observational field, the researchers' dual roles, cost versus benefit, impact of culture, religion and ethnicity, and the determination of research limits/boundaries, with reflections from the authors' own experiences used to exemplify the issues.     

Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors

Adhesive interactions with the extracellular matrix of the bone marrow (BM) stroma are of critical importance in the regulation of hematopoiesis. In part, these interactions are presumed to play an important role in retaining CD34+ hematopoietic progenitor cells (HPCs) within the BM environment, in close proximity with BM stromal cells and the cytokines they produce. Evidence of a more direct role for cell adhesion in the regulation of hematopoiesis is provided by recent data showing that adhesive interactions can also provide important costimulatory signals. We have previously shown that normal CD34+ HPCs express high levels of fibronectin (Fn) receptors very late antigen-4 (VLA-4) and VLA-5 in a low-affinity state, which do not allow HPCs to strongly adhere on immobilized Fn, and that cytokines such as interleukin-3, granulocyte-monocyte colony-stimulating factor, and stem cell factor transiently activate these receptors, providing HPCs with an adhesive phenotype on Fn. Thus, knowledge of the functional states of adhesion receptors is critical to our understanding of the physiological mechanisms responsible for the regulation of normal hematopoiesis. Herein, we show that combinations of cytokines that synergize to stimulate the proliferation of CD34+ HPCs result in additive stimulation of the adhesion of these cells to Fn. Thus, the activation level of Fn receptors expressed by normal CD34+ HPCs is highly correlated with their proliferative state, suggesting a functional link between these two events. Therefore, we propose a 2- step model with an initial activation of VLA-4 and VLA-5 generated by cytokine receptors that is followed by a secondary signal resulting from Fn binding to VLA-4 and VLA-5, which may cooperate with those generated by cytokine receptors.     

Living and dying: responsibility for end‐of‐life care in care homes without on‐site nursing provision ‐ a prospective study

The aim of the study was to describe the expectations and experiences of end‐of‐life care of older people resident in care homes, and how care home staff and the healthcare practitioners who visited the care home interpreted their role. A mixed‐method design was used. The everyday experience of 121 residents from six care homes in the East of England were tracked; 63 residents, 30 care home staff with assorted roles and 19 National Health Service staff from different disciplines were interviewed. The review of care home notes demonstrated that residents had a wide range of healthcare problems. Length of time in the care homes, functional ability or episodes of ill‐health were not necessarily meaningful indicators to staff that a resident was about to die. General Practitioner and district nursing services provided a frequent but episodic service to individual residents. There were two recurring themes that affected how staff engaged with the process of advance care planning with residents; ‘talking about dying’ and ‘integrating living and dying’. All participants stated that they were committed to providing end‐of‐life care and supporting residents to die in the care home, if wanted. However, the process was complicated by an ongoing lack of clarity about roles and responsibilities in providing end‐of‐life care, doubts from care home and primary healthcare staff about their capacity to work together when residents’ trajectories to death were unclear. The findings suggest that to support this population, there is a need for a pattern of working between health and care staff that can encourage review and discussion between multiple participants over sustained periods of time.     

Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings

Computed tomography (CT) was compared with chest radiography in the assessment of disease severity in 27 patients with sarcoidosis. The CT scans and radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by visual scoring (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification. The severity of parenchymal changes on the CT scan and on the radiograph was significantly correlated with the severity of dyspnea (r = .61 and .58, respectively; P less than .001), diffusing capacity (r = -.62 and -.52, P less than .01), and vital capacity (r = -.49 and -.51, P less than .01). Patients with predominantly irregular opacities had more severe dyspnea and lower lung volumes than patients with predominantly nodular opacities (P less than .05). The authors conclude that in patients with sarcoidosis, the radiographic and CT assessments of disease severity show similar correlation with clinical and functional impairment.